KIT

Identity

Other names	SCFR (Stem Cell Factor Receptor)
	CD117
Hugo	KIT
Location	4q12
Local_order	centromere-PDGFRA -KIT-KDR-telomere
	KIT (4q12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

DNA/RNA

Description	spans 89 kb; 21 exons; size of intron 1 : 37,4 kb
Transcription	5,23 kb mRNA; alternative splicing of exon 9 gives rise to two isoforms, KitA and Kit, that differ by the presence or absence of four aminoacids.

Protein

Description	976 aa; 145 kDa; type III receptor tyrosine kinase; contains an extracellular domains with 5 Ig-like loops, a highly hydrophobic transmenbrane domain (23 aa), and an intracellular domain with tyrosine kinase activity split by a kinase insert (KI) in an ATP-binding region and in the phosphotransferase domain
Expression	hematopoietic stem cells, mast cells, melanocytes, germ-cell lineages and ICCs (Interstitial cells of Cajal).
Localisation	plasma membrane
Function	SCF/MGF receptor with tyrosine kinase activity; binding of ligand (SCF) induces receptor dimerization, autophosphorylation and signal transduction via molecules containing SH2- domains.
Homology	with CSF-1R, PDGFRb, PDGFRa, and FLT3.

Mutations

Note	see diagrams: Loss-of-function mutations, and Gain-of-function mutations
Germinal	in piebaldism, and in familial gastrointestinal stromal tumours (see below).
Somatic	in aggressive mastocytosis, mast cell leukemia, ANLL with/without mast cell involvement, myeloproliferative disorders, colon carcinoma and gastrointestinal stromal tumours and germ cell tumors (GCCs)

Implicated in

Entity	Piebaldism.
Disease	autosomal dominant disorder of pigmentation; loss of function abnormalities of the c-kit gene have been demonstrated in 59% of the typical patients.
Entity	Familial gastrointestinal stromal tumours and sporadic gastrointestinal stromal tumours (GISTs).
Disease	GISTs are the most common mesenchymal tumors in the human digestive tract; they originate from kit-expressing cells (ICCs), and often have activating c-kit mutations clustered in the juxtamembrane domain.
Entity	systemic mast cell disease (SMCD)
Disease	mast cell hyperplasia in the bone marrow, liver, spleen, lymph nodes, gastrointestinal tract and skin; gain of function mutations are detected in most patients
Prognosis	depending on the four clinical entities recognized: indolent form, form associated with hematologic disorder, aggressive SMCD and mast cell leukemia; leukemic transformation with mast cell involvement is characterized by rapid progression of disease with a survival time less than 1 year
Oncogenesis	clinical features of malignant hematopoietic cell growth are influenced by the time, the location of c-kit mutative events, and the number of associated lesions.
Entity	Core binding factor leukemias (ANLL-M2 with t(8;21) (link), (ANLL-M4Eo with inv(16))
Disease	characterized by disruption and loss of CBFa2/AML1 - CBFb/PEBP2b function. Myelomonoblastic leukemia cells are marked by combined positivity for the stem cell antigens CD34, CD117 and high frequency of c-kit mutations ( see Figure on CBF leukemia and KIT mutations)

To be noted

loss of expression of c-KIT appears to be associated with progression of some tumors (melanoma) and autocrine/paracrine stimulation of the c-kit/SCF system may participate in human solid tumors such as lung, breast, testicular and gynecological malignancies.

External links

	Nomenclature
Hugo	KIT
GDB	KIT
Entrez_Gene	KIT  3815  v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
	Cards
Atlas	KITID127
GeneCards	KIT
Ensembl	KIT [Search_View]   ENSG00000157404 [Gene_View]
Genatlas	KIT
GeneLynx	KIT
eGenome	KIT
euGene	3815
	Genomic and cartography
GoldenPath	KIT  -  4q12   chr4:55218852-55301638 +  4q11-q12    (hg18-Mar_2006)
Ensembl	KIT - 4q11-q12 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	KIT
	Gene and transcription
Genbank	AJ438313 [ ENTREZ ]
Genbank	BC071593 [ ENTREZ ]
Genbank	CN414753 [ ENTREZ ]
Genbank	DC376760 [ ENTREZ ]
Genbank	X06182 [ ENTREZ ]
RefSeq	NM_000222 [ SRS ]    NM_000222 [ ENTREZ ]
RefSeq	NM_001093772 [ SRS ]    NM_001093772 [ ENTREZ ]
RefSeq	AC_000047 [ SRS ]    AC_000047 [ ENTREZ ]
RefSeq	NC_000004 [ SRS ]    NC_000004 [ ENTREZ ]
RefSeq	NT_022853 [ SRS ]    NT_022853 [ ENTREZ ]
RefSeq	NW_922162 [ SRS ]    NW_922162 [ ENTREZ ]
AceView	KIT AceView - NCBI
Unigene	Hs.479754 [ SRS ]    Hs.479754 [ NCBI ]     HS479754 [ spliceNest ]
Fast-db	4404 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P10721 [ SRS]    P10721 [ EXPASY ]     P10721 [ INTERPRO ]
Prosite	PS50835 IG_LIKE [ SRS ]    PS50835 IG_LIKE [ Expasy ]
Prosite	PS00107 PROTEIN_KINASE_ATP [ SRS ]    PS00107 PROTEIN_KINASE_ATP [ Expasy ]
Prosite	PS50011 PROTEIN_KINASE_DOM [ SRS ]    PS50011 PROTEIN_KINASE_DOM [ Expasy ]
Prosite	PS00109 PROTEIN_KINASE_TYR [ SRS ]    PS00109 PROTEIN_KINASE_TYR [ Expasy ]
Prosite	PS00240 RECEPTOR_TYR_KIN_III [ SRS ]    PS00240 RECEPTOR_TYR_KIN_III [ Expasy ]
Interpro	IPR013151 Ig [ SRS ]    IPR013151 Ig [ EBI ]
Interpro	IPR007110 Ig-like [ SRS ]    IPR007110 Ig-like [ EBI ]
Interpro	IPR013783 Ig-like_fold [ SRS ]    IPR013783 Ig-like_fold [ EBI ]
Interpro	IPR003599 Ig_sub [ SRS ]    IPR003599 Ig_sub [ EBI ]
Interpro	IPR003598 Ig_sub2 [ SRS ]    IPR003598 Ig_sub2 [ EBI ]
Interpro	IPR000719 Prot_kinase_core [ SRS ]    IPR000719 Prot_kinase_core [ EBI ]
Interpro	IPR001824 Recept_tyr_kinase-III_CS [ SRS ]    IPR001824 Recept_tyr_kinase-III_CS [ EBI ]
Interpro	IPR001245 Tyr_pkinase [ SRS ]    IPR001245 Tyr_pkinase [ EBI ]
Interpro	IPR008266 Tyr_pkinase_AS [ SRS ]    IPR008266 Tyr_pkinase_AS [ EBI ]
Interpro	IPR009134 VEGFR_N [ SRS ]    IPR009134 VEGFR_N [ EBI ]
CluSTr	P10721
Pfam	PF00047 ig [ SRS ]    PF00047 ig [ Sanger ]    pfam00047 [ NCBI-CDD ]
Pfam	PF07714 Pkinase_Tyr [ SRS ]    PF07714 Pkinase_Tyr [ Sanger ]    pfam07714 [ NCBI-CDD ]
Smart	SM00409 IG [EMBL]
Smart	SM00408 IGc2 [EMBL]
Smart	SM00219 TyrKc [EMBL]
Prodom	PD000001 Prot_kinase[INRA-Toulouse]
Prodom	P10721 KIT_HUMAN [ Domain structure ]   P10721 KIT_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	P10721
PDB	1PKG [ SRS ]    1PKG [ PdbSum ],   1PKG [ IMB ]   1PKG [ RSDB ]
PDB	1QZJ [ SRS ]    1QZJ [ PdbSum ],   1QZJ [ IMB ]   1QZJ [ RSDB ]
PDB	1QZK [ SRS ]    1QZK [ PdbSum ],   1QZK [ IMB ]   1QZK [ RSDB ]
PDB	1R01 [ SRS ]    1R01 [ PdbSum ],   1R01 [ IMB ]   1R01 [ RSDB ]
PDB	1T45 [ SRS ]    1T45 [ PdbSum ],   1T45 [ IMB ]   1T45 [ RSDB ]
PDB	1T46 [ SRS ]    1T46 [ PdbSum ],   1T46 [ IMB ]   1T46 [ RSDB ]
PDB	2E9W [ SRS ]    2E9W [ PdbSum ],   2E9W [ IMB ]   2E9W [ RSDB ]
PDB	2EC8 [ SRS ]    2EC8 [ PdbSum ],   2EC8 [ IMB ]   2EC8 [ RSDB ]
HPRD	01287
	Protein Interaction databases
DIP	P10721
IntAct	P10721
	Polymorphism : SNP, mutations, diseases
OMIM	164920;172800;273300;601626;606764    [ map ]
GENECLINICS	164920;172800;273300;601626;606764
SNP	KIT [dbSNP-NCBI]
SNP	NM_000222 [SNP-NCI]
SNP	NM_001093772 [SNP-NCI]
SNP	KIT [GeneSNPs - Utah]  KIT] [HGBASE - SRS]
HAPMAP	KIT [HAPMAP]
COSMIC	KIT [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	KIT
	General knowledge
Family Browser	KIT [UCSC Family Browser]
SOURCE	NM_000222
SOURCE	NM_001093772
SMD	Hs.479754
SAGE	Hs.479754
Enzyme	2.7.10.1 [ Enzyme-SRS ]   2.7.10.1 [ Brenda-SRS ]   2.7.10.1 [ KEGG ]   2.7.10.1 [ WIT ]
GO	nucleotide binding [Amigo]  nucleotide binding
GO	receptor signaling protein tyrosine kinase activity [Amigo]  receptor signaling protein tyrosine kinase activity
GO	receptor activity [Amigo]  receptor activity
GO	stem cell factor receptor activity [Amigo]  stem cell factor receptor activity
GO	vascular endothelial growth factor receptor activity [Amigo]  vascular endothelial growth factor receptor activity
GO	protein binding [Amigo]  protein binding
GO	ATP binding [Amigo]  ATP binding
GO	protein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GO	protein amino acid dephosphorylation [Amigo]  protein amino acid dephosphorylation
GO	signal transduction [Amigo]  signal transduction
GO	transmembrane receptor protein tyrosine kinase signaling pathway [Amigo]  transmembrane receptor protein tyrosine kinase signaling pathway
GO	protein kinase cascade [Amigo]  protein kinase cascade
GO	spermatogenesis [Amigo]  spermatogenesis
GO	positive regulation of cell proliferation [Amigo]  positive regulation of cell proliferation
GO	response to radiation [Amigo]  response to radiation
GO	external side of plasma membrane [Amigo]  external side of plasma membrane
GO	membrane [Amigo]  membrane
GO	integral to membrane [Amigo]  integral to membrane
GO	transferase activity [Amigo]  transferase activity
GO	peptidyl-tyrosine phosphorylation [Amigo]  peptidyl-tyrosine phosphorylation
GO	cytokine and chemokine mediated signaling pathway [Amigo]  cytokine and chemokine mediated signaling pathway
GO	hemopoiesis [Amigo]  hemopoiesis
GO	positive regulation of MAP kinase activity [Amigo]  positive regulation of MAP kinase activity
GO	pigmentation during development [Amigo]  pigmentation during development
GO	epithelial cell proliferation [Amigo]  epithelial cell proliferation
BIOCARTA	Regulation of BAD phosphorylation    [Genes]
BIOCARTA	Melanocyte Development and Pigmentation    [Genes]
KEGG	Cytokine-cytokine receptor interaction
KEGG	Hematopoietic cell lineage
PubGene	KIT
TreeFam	KIT
	Other databases
	Probes
Probe	Cancer Cytogenetics (Bari)
Probe	KIT Related clones (RZPD - Berlin)
	PubMed
PubMed	250 Pubmed reference(s) in LocusLink

Bibliography

Cloning and structural analysis of the human c-kit gene.

Vandenbark GR, deCastro CM, Taylor H, Dew-Knight S, Kaufman RE

Oncogene. 1992 ; 7 (7) : 1259-1266.

PMID 1377810

Novel mutations and deletions of the KIT (steel factor receptor) gene in human piebaldism.

Ezoe K, Holmes SA, Ho L, Bennett CP, Bolognia JL, Brueton L, Burn J, Falabella R, Gatto EM, Ishii N

American journal of human genetics. 1995 ; 56 (1) : 58-66.

PMID 7529964

Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm.

Longley BJ, Tyrrell L, Lu SZ, Ma YS, Langley K, Ding TG, Duffy T, Jacobs P, Tang LH, Modlin I

Nature genetics. 1996 ; 12 (3) : 312-314.

PMID 8589724

Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes.

Andre C, Hampe A, Lachaume P, Martin E, Wang XP, Manus V, Hu WX, Galibert F

Genomics. 1997 ; 39 (2) : 216-226.

PMID 9027509

Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.

Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y

Science (New York, N.Y.). 1998 ; 279 (5350) : 577-580.

PMID 9438854

C-kit gene abnormalities in gastrointestinal stromal tumors (tumors of interstitial cells of Cajal.

Sakurai S, Fukasawa T, Chong JM, Tanaka A, Fukayama M

Japanese journal of cancer research : Gann. 1999 ; 90 (12) : 1321-1328.

PMID 10665649

c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia.

Gari M, Goodeve A, Wilson G, Winship P, Langabeer S, Linch D, Vandenberghe E, Peake I, Reilly J

British journal of haematology. 1999 ; 105 (4) : 894-900.

PMID 10554798

Activating c-kit gene mutations in human germ cell tumors.

Tian Q, Frierson HF Jr, Krystal GW, Moskaluk CA

The American journal of pathology. 1999 ; 154 (6) : 1643-1647.

PMID 10362788

Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis.

Longley BJ Jr, Metcalfe DD, Tharp M, Wang X, Tyrrell L, Lu SZ, Heitjan D, Ma Y

Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (4) : 1609-1614.

PMID 9990072

KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors.

Lux ML, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri G, Xiao S, Singer S, Fletcher CD, Fletcher JA

The American journal of pathology. 2000 ; 156 (3) : 791-795.

PMID 10702394

C-kit mutations in core binding factor leukemias.

Beghini A, Peterlongo P, Ripamonti CB, Larizza L, Cairoli R, Morra E, Mecucci C

Blood. 2000 ; 95 (2) : 726-727.

PMID 10660321

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Contributor(s)

Written	09-1998	Lidia Larizza and Alessandro Beghini

Citation

This paper should be referenced as such :

Larizza L and Beghini A . KIT. Atlas Genet Cytogenet Oncol Haematol. September 1998 . URL : http://AtlasGeneticsOncology.org/Genes/KITID127.html

Larizza L and Beghini A . KIT. Atlas Genet Cytogenet Oncol Haematol. . URL : http://AtlasGeneticsOncology.org/Genes/KITID127.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon May 12 18:05:29 2008